Modeling the molecular bases of glucose metabolism in astrocytes

Glutamate released in the synaptic cleft during neuronal activity is removed by surrounding astrocytes. One of the roles of the glutamate clearance by astrocytes is triggering a cascade of molecular events that provides metabolic substrates to neurons. Glutamate is co-transported with three sodium ions by amino acid transporters expressed in astrocytes, inducing an intracellular ionic sodium elevation. The consequence of this increase is the activation of the increasing of the energy demand in astrocytes. Astrocytes can also release glutamate. Recently it has been shown that glutamate is released in association with calcium ions waves, which represent a form of multicellular bidirectional communication with neurons. We present a novel model of the molecular bases of the glucose metabolism in astrocytes, taking into account the presence of calcium and sodium oscillations in the cell. We calibrate the model on real Positron Emission Tomography images of normal subjects to estimate the kinetic rate constants of the biochemical interactions driving the metabolism.